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Chapter 3 : The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity

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Abstract:

This chapter presents the basic principles of the immune response of the host through the innate and adaptive immune systems, particularly as they relate to bacterial infection. Host-bacterium relationships may be altered by antibacterial drugs in three major ways: alteration of the tissue response, alteration of the immune response, and alteration of the microbial flora. The immune system consists of innate immunity and adaptive immunity. The function of the complement system (C3b) is discussed in the chapter. The major antigen-presenting cells (APCs) populations in the immune system are composed of mononuclear phagocytes and dendritic cells. Antibodies (immunoglobulins) are a group of glycoproteins present in the blood serum and tissue fluids of mammals, which can combine with antigenic determinants. Secretory immunoglobulin A (IgA) is the primary antibody of the secretory immune system. This system is found in the gastrointestinal tract, upper and lower respiratory tracts, and genitourinary system. Secretory IgA is also found in saliva, tears, and breast milk. Phagocytes have an intrinsic ability to bind directly to microorganisms via nonspecific cell surface receptors, form phagosomes, and digest the microorganisms. This phagocytic process can be greatly enhanced by opsonization by the complement component C3b or by both antibody and C3b. In order to be cured of a bacterial infection, a patient must have an operative immunological defense mechanism (i.e., must be immunocompetent). If antibacterial therapy is given, it will help fight invading bacteria; however, antibacterials alone, without the contribution of the immune response, are seldom able to overcome an infection.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figures

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Figure 3.1

Innate and adaptive immunity. The mechanisms of innate immunity provide the initial defense against infections. Only selected mechanisms are shown; for example, the complement system, an important component of the innate immunity, is not included. The kinetics of the innate and adaptive immunity are approximations and may vary in different infections. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Image of Figure 3.2
Figure 3.2

Structure of a class I MHC molecule. The schematic diagram (left) illustrates the different regions of the MHC molecule (not drawn to scale). Class I molecules are composed of a polymorphic 〈chain noncovalently attached to nonpolymorphic β2-microglobulin. The 〈chain contains glycosylated carbohydrate residues (not shown). The ribbon diagram (right) shows the structure of the extracellular portion of the HLA-B27 molecule resolved by X-ray crystallography. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.\

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.3

Structure of a class II MHC molecule. The schematic diagram (left) illustrates the different regions of the MHC molecule (not drawn to scale). Class II molecules are composed of a polymorphic α chain noncovalently attached to a polymorphic β chain. Both chains contain glycosylated carbohydrate residues (not shown). The ribbon diagram (right) shows the structure of the extracellular portion of the HLA-DR1 molecule resolved by Xray crystallography. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.4

Hematopoiesis. The development of the different lineages of blood cells is depicted in this “hematopoietic tree.” Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.5

Overall view of the lymphatic system, showing the locations of major organs.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.6

Classes of lymphocytes. B lymphocytes recognize soluble antigens and develop into antibody-secreting cells. Helper T lymphocytes recognize antigens on the surface of host accessory cells and secrete cytokines, which stimulate different mechanisms of immunity and inflammation. Cytolytic T lymphocytes recognize antigens on target cells and lyse these targets. NK cells use receptors that are not fully identified to recognize and lyse targets. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Image of Figure 3.7
Figure 3.7

Bidirectional molecular interactions between B and T lymphocytes. In the model for the role of multiple ligand-receptor pairs in T-cell-dependent B-cell activation, helper T cells recognize the antigen in the form of peptide-MHC complexes, CD40 ligand then binds to CD40 receptors in the B cells, and together with the liberation of cytokines mediated by T cells, B cells initiate proliferation and differentiation. B7-1 and B7-2 are now designated CD80 and CD86, respectively. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.8

Accessory molecules of T lymphocytes. The interaction of a CD4+ helper T cell with an APC or of a CD8+ cytolytic T lymphocyte (CTL) with a target cell involves multiple Tcell membrane proteins that recognize different ligands on the APC or target cell. Abbreviations: ICAM-1, intercellular cell adhesion molecule 1; LFA-1, lymphocyte function antigen 1. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.9

Phases of T-cell responses. In the recognition and activation phases of T-cell responses, antigen recognition by a T cell, in this case a naive CD4+ cell, induces cytokine (e.g., IL-2) secretion, clonal expansion as a result of IL-2-induced autocrine cell proliferation, and differentiation of the T cells into effector cells or memory cells. In the effector phase of the response, the effector cell responds to antigen by producing cytokines that have several actions, such as activation of macrophages, B lymphocytes, and CD8+ T cells and induction of inflammation. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Image of Figure 3.10
Figure 3.10

Schematic diagram of an antibody (Ig) molecule. Within the antibody unit structure, intrachain disulfide bonds create loops that form domains. All light chains contain a single variable domain (VL) and a single constant domain (CL). Heavy chains contain a variable domain (VH) and either three or four constant domains (CH1, CH2, CH3, and CH4). Reprinted from L. M. Prescott, J. P. Harley, and D. A. Klein, Microbiology, 4th ed. (McGraw-Hill, Boston, Mass., 1999), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.11

Interactions between domains in the separate chains of an Ig molecule are critical to its quaternary structure. (a) Model of an IgG molecule based on X-ray crystallographic analysis, showing the association between domains. Each solid ball represents an amino acid; the larger balls represent carbohydrate. (b) A schematic diagram showing the interacting heavy- and light-chain domains. Note that the CH2/CH2 domains protrude because of the presence of carbohydrate in the interior. CDRs, complementaritydetermining regions. Reprinted from R. A. Goldsby, T. J. Kindt, and B. A. Osborne, Kuby Immunology, 4th ed. (W. H. Freeman & Co., New York, N.Y., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Image of Figure 3.12
Figure 3.12

General structures of the four subclasses of human IgG, which differ in the number and arrangement of interchain disulfide bonds (thick black lines) linking the heavy chains. A notable feature of human IgG3 is its 11 interchain disulfide bonds. Reprinted from R. A. Goldsby, T. J. Kindt, and B. A. Osborne, Kuby Immunology, 4th ed. (W. H. Freeman & Co., New York, N.Y., 2000), with permission from the publisher. Masc_03 7/7

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Image of Figure 3.13
Figure 3.13

General structures of the four subclasses of human IgG, which differ in the number and arrangement of interchain disulfide bonds (thick black lines) linking the heavy chains. A notable feature of human IgG3 is its 11 interchain disulfide bonds. Reprinted from R. A. Goldsby, T. J. Kindt, and B. A. Osborne, Kuby Immunology, 4th ed. (W. H. Freeman & Co., New York, N.Y., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.14

Overview of complement activation (see the text for an explanation). Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.15

Schematic diagram of the opsonization of a bacterium. Reprinted from L. M. Prescott, J. P. Harley, and D. A. Klein, Microbiology, 4th ed. (McGraw-Hill, Boston, Mass., 1999), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.16

Specific immune response to extracellular bacteria. Reprinted from A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunobiology, 4th ed. (The W. B. Saunders Co., Philadelphia, Pa., 2000), with permission from the publisher.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Figure 3.17

Schematic presentation of the major host defense mechanisms against bacteria.

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
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Tables

Generic image for table
Table 3.1

Selected important cytokines

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
Generic image for table
Table 3.2

Examples of bacteria commonly associated with extracellular disease a

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3
Generic image for table
Table 3.3

Major infections of humans caused by facultative and obligate intracellular bacteria a

Citation: Mascaretti O. 2003. The Immune System: an Overview Immunodeficiencies Immunocompromised Hosts Innate Immunity, p 43-67. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch3

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